The Interrelationship of Growth Hormone (GH)-Releasing Factor and Somatostatin in Generation of the Ultradian Rhythm of GH Secretion*

Abstract

To further delineate the relationship between GH[growth hormone]-releasing (GRF) and somatostatin (SRIF) in generation of the ultradian rhythm of GH secretion, 2 GRF peptides, human pancreas (hp) GRF-44 and rat hypothalamic (rh) GRF were used, and their interaction with SRIF were studied by passive immunization with a specific antiserum (AS) to SRIF. Freely moving, chronically cannulated male rats were given 10 .mu.g of either hpGRF-44 or rhGRF i.v. during peak (1100 h) and trough (1300 h) periods of the GH rhythm. Six hour plasma GH profiles were obtained after pretreatment with either SRIF AS or normal sheep serum (NSS) as a control. In NSS-treated rats, the plasma GH responses to both hpGRF-44 and rhGRF were significantly greater when the peptides were administered during peak than during trough periods. Immunoneutralization with SRIF AS eliminated these differences and permitted marked GH release in response to both peptides at 1300 h. In addition, SRIF AS augmented the GRF-induced GH response at 1100 h compared with that in NSS controls. The rhGRF peptide caused significantly more GH release than hpGRF under both conditions. The GH-releasing abilities of the GRF peptides vary markedly according to the time of injection; the weak GRF-induced GH response observed during trough periods of the GH rhythm apparently is due to antagonization by endogenous circulating SRIF; and the rat-derived GRF may be a more potent GH secretagogue than the human-derived peptide in the rat. GRF and SRIF are secreted tonically from the hypothalamus into the hypophyseal portal blood, and superimposed upon this steady state release is an additional 3-4 h rhythmic surge of each peptide, providing for integration of the ultradian rhythm of GH secretion, as observed in peripheral blood.